BENGALURU: After more than 10 years of research, scientists from the Jawaharlal Nehru Centre for Advanced Scientific Research (
) have developed a
that can prevent the mechanism that results in
(brain cells) becoming dysfunctional in Alzheimer’s disease (AD).
The team led by professor T Govindaraju is confident that the molecule, christened TGR63, could be a
potential drug candidate
to halt or cure the leading cause of dementia. “We are preparing for clinical trials and are looking to partner with pharma firms both in India and outside,” Govindaraju told TOI.
Stating that in the Alzheimer’s brain, abnormal levels of naturally forming
together to form plaques that collect between neurons and disrupt cell function, Govindraju said this is caused by production and deposition of a protein called amyloid peptide (Aβ) that accumulates in the central nervous system.
“The multifactorial nature of AD, attributed to multifaceted amyloid toxicity, has kept researchers from developing effective treatment. Now, we have designed and synthesized a set of novel small molecules and identified a lead candidate which they found could reduce the Aβ toxicity,” he explained.
He said that detailed studies have established TGR63 to rescue neuronal cells from amyloid toxicity. Remarkably, he said, the molecule was also found to reduce amyloid burden in the cortex and hippocampus, or a complex part embedded deep into the temporal lobe, thereby reversing cognitive decline. This research has been published recently in the journal Advanced Therapeutics.
“Any treatment relating to the brain has a major challenge in breaking the blood-brain barrier which prevents drugs from reaching the brain. In this case, TGR63 manages to break this and enter the brain,” he said.
He added that while available treatments provide temporary relief, there are no approved drugs that directly act on the disease mechanisms of AD. He pointed out that while the incidence, and especially deaths of most major diseases like cancer are on the decline globally, AD has registered an increase of 71%. Thus, there is an unmet need to develop drug candidates to halt or cure Alzheimer’s disease.
“During our studies, mice brains affected with AD, when treated with TGR63 showed a significant reduction of amyloid deposits, validating its therapeutic efficacy. The mice also showed reduction of learning deficiency, memory impairment, and cognitive decline as revealed by distinct behavioural tests. These key attributes have validated the potential of TGR63 as a promising drug candidate for the treatment of AD,” Govindaraju said.